Methods for the integrated synthesis and purification of oligonucleotides
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United States of America Patent
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Aug 29, 2006
Grant Date -
Oct 16, 2003
app pub date -
Jan 22, 2003
filing date -
Jan 23, 2002
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Abstract
The present invention discloses novel methods for the integrated synthesis and purification of oligonucleotides. The methods employ novel capping reagents carrying two functional groups. The first functional group provides for a smooth and efficient capping process and incorporates the second functional group into contaminant oligonucleotides during solid phase oligonucleotide synthesis. The second functional group functions as a chemical purification handle in the trapping of truncated oligonucleotides (failure sequences) on a solid support. The trapping process creates covalent bonds between the solid support and the truncated oligonucleotides and therefore allows the removal of the truncated sequences from the desired full length oligonucleotide product by filtration. The chemical trapping process employed in this invention is based on cycloaddition reactions, particularly Diels-Alder reactions between the truncated oligonucleotides and the trapping agent. The invention includes novel solid support compositions that carry covalently attached Diels-Alder reaction components.
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